1. Field:
The invention relates to processes for producing vaccines against pathogens and to the vaccines produced thereby. For the purpose of this invention, a pathogen includes but is not limited to disease-causing organisms, viruses, some normal cells, abnormal cells, and any products or parts thereof.
2. State of the Art
In general, a vaccine is any material which induces an organism to acquire immunity against disease. Effective vaccines work by triggering an organism's normal immunological responses against a disease, but, at the same time, do not themselves cause the disease. In other words, a vaccine will typically have the antigenic determinants of a pathogen, but not the pathogenic properties. Once on organism's immunological responses against a disease are triggered, the organism starts producing disease-fighting agents. When the titer of disease-fighting agents reach a certain level, the organism acquires an immunity against the disease.
Many forms of vaccines against viral-caused diseases have been used. The most efficacious virus vaccines have been developed by attenuating disease-causing viruses. For example, attenuation of the Marek's disease virus (MDV) has worked as vaccine for chickens. In humans, attenuated polio and measles viruses have worked as vaccines.
Studies on oncogenic viruses in animal systems have been done. Some attenuated oncogenic viruses have been found to immunize, while other fail. The use of killed avian sarcoma virus as a vaccine has been shown to be ineffective in preventing tumors in chickens. In the murine RNA tumor virus system, however, immunization of mice with an inactivated leukemia virus prevented leukemia when challenged with the same live virus, and formalin-killed mammary tumor virus afforded some protection from challenge by the live virus.
Attenuated viruses have been used as a vaccine in the murine leukemia virus system. It was found that live, non-oncogenic murine leukemia viruses, when inoculated into newborn mice, protected the mice from development of leukemia after challenge with highly oncogenic Gross leukemia virus. Cells infected by non-oncogenic, yet antigenic, murine leukemia viruses also protected the animal from tumors produced by the virulent parent virus. Similar studies have been conducted with the radiation leukemia virus. The thymotropic radiation leukemia virus appears to lose its oncogenicity when grown in tissue culture on fibroblasts, yet still retains its antigenicity. Mice were successfully immunized with this attenuated virus. It also has been shown that the radiation leukemia virus can protect an animal from radiation-virus-induced lymphoma cells. Likewise, a benign bone tumor virus protects against a malignant bone tumor virus cancer induction. Immunization with infectious avian leukosis virus has also rendered chickens resistant to tumor development on challenge with avian sarcoma virus. Successful results have been obtained by immunizing against virus-induced leukemia by leukemic cell suspension. Avian leukosis viruses, used as live vaccines, have been shown to protect animals in vivo from sarcomagenesis. It has been shown that the avian and murine leukosis virus of different subgroups can protect an animal from tumor virus induced tumorigenesis. A particular murine leukemia virus in the Friend virus complex has been shown to cause spontaneous regression of the leukemia.
The major drawback with using an attenuated, disease-causing virus as a vaccine is the possibility that a small percentage of the vaccine will not be attenuated and that, therefore, the vaccine will induce the disease instead of immunity upon vaccination. This is especially a problem with vaccines against oncogenic viruses, because none of the attenuated viruses have been shown to be deleted of the oncogenic gene regions and, thus, all are potentially oncogenic. Furthermore, naked deoxyribonucleic acid (DNA) cannot be used as an antigen since it has been shown to produce malignant tumors in vivo. In addition, enhancement of tumorigenesis was noted in two carcinogenesis systems and in one murine sarcoma virus system where an attenuated virus was the vaccine. Another problem with attenuated virus vaccines is that the attenuation involves single nucleotide base changes which can and have reverted back to the pathogen.
Other types of vaccines have been developed by vaccinating with material which has the same or similar antigenic properties of a pathogen. Having the same antigenicity as the pathogen, the material will trigger an immunological response which will immunize against the pathogen. For example, the turkey herpes virus (HVT) is used as a vaccine against Marek's disease, and subunit vaccines have also been successful. The problems with these types of vaccines are numerous. First, it is often difficult to identify and isolate a material with the same antigenic properties as the pathogen, and subunits are difficult to obtain in large quantity. Further, such material may induce a cross-immununity for non-disease-causing agents or substances which are beneficial to the immunized organism.